Abstract

Inwardly rectifying potassium channels (Kir channels) are important for neuronal signalling and membrane excitability. In the present work we characterized, for the first time, Kir channels in rat dopaminergic (DA) periglomerular (PG) cells, interneurons located at the entry of the bulbar circuitry whose role is not yet well defined, using patch-clamp techniques.
Whole-cell currents mediated by Kir channels were recorded in DA-PG cells either in thin slices or enzymatically dissociated. They could be distinguished from the hyperpolarization-activated current (Ih) by showing full activation in < 10 ms, no inactivation, and being suppressed by 300 µM Ba2+ in a typical voltage-dependent manner. The KIR current amplitude is affected by temperature, with a Q10 of about 1.7, and its reversal potential is nearly coincident with EK. Its blockage by Ba2+ entailed a large depolarization (about ?? mV), leading to the end of any spontaneous activity; in addition, Ba2+ (200 µM) also induce a 17.79 ± 3.23% increase in input resistance .
The depolarization induced by Ba2+ is sufficient to block the spontaneous activity of DA-PG cells, although the KIR current is not an essential component of the pacemaker machinery, as the injection of a hyperpolarising current under Ba2+ block restore normal firing.
The current is insensitive to tertiapine (100 nM) and is modulated by intracellular concentration of cAMP, as shown by a 14% decrease induced by forskolin (10 µM, +0.1 mM IBMX). We have also tested the neuromodulatory effects of the activation of several metabotropic receptors which are known to be present on these cells, showing that the current is controlled in both directions by a multiplicity of pathways, whose activation in some case increase the amplitude of the current, as muscarinic (oxotremorine, 100 µM), noradrenergic (noradrenaline 100 µM, + 1 mM ascorbic acid) and GABAergic (100 µM) paths, whereas other have the opposite effect, as D2 agonists (quinpirole, 30 µM), 5-HT (50 µM) and histamine (10 µM).
Interestingly, a parallel study conducted on the h-current in the same preparation has shown an almost specular effect: the current, which has a depolarising effect, is positively modulated by cAMP (forskolin 10 µM and 0.1 mM IBMX) and negatively by noradrenaline (100 µM + 1 mM ascorbic acid).
It can be speculated that, in the main olfactory bulb, a given pathway controlled by neurotransmitters plays important roles in activating and reconfiguring neural networks to allow behavioural flexibility. While the net effects of a neuromodulator change the network in a particular direction, this study reveals cases where a given neuromodulator activate functionally opposing mechanisms on a single neuron. One important benefit of opposing modulatory actions may be to stabilize the modulated state of the network while adding flexibility, and to prevent it from being overmodulated and becoming non-functional